Indocyanine green fluorescence visualizes landmark arteries for endoscopic sinus and skull base surgery.

OBJECTIVE: Landmark arteries during endoscopic sinus surgery are currently identified on the basis of anatomy, CT imaging and navigation, and Doppler flowmetry. However, the advantage of intraoperative fluorescence imaging during endoscopic sinus surgery has not been demonstrated. This study aimed to investigate whether Indocyanine Green (ICG) is useful for visualizing landmark arteries during endoscopic sinus and skull base surgery. METHODS: Eight patients who underwent endoscopic sinus and pituitary surgeries and consented to study participation were included. After planned procedures were performed as usual, landmark arteries were examined by ICG endoscope. Recorded video and preoperative CT images were analyzed for identification of five landmark arteries: anterior ethmoidal artery (AEA), posterior ethmoidal artery (PEA), internal carotid artery (ICA), sphenopalatine artery (SPA), and postnasal artery (PNA). Identification of arteries was evaluated three grades: identifiable, locatable, unrecognizable. RESULTS: Eight patients and eleven sides were evaluated. The ICG dose was 2.5 mg/body and a single shot was sufficient for evaluation. 100 % of AEA was identified (9/9 sides), 86 % of PNA (6/7 sides), 56 % of ICA (5/9 sides), and 25 % of PEA and SPA (2/8 sides). CONCLUSION: ICG could visualize landmark arteries, even thin arteries like AEA, during endoscopic sinus and skull base surgeries. Visualization was affected by thickness of bone or soft tissue above arteries, blood clots, sensitivity setting, and angle and distance of near-infrared light irradiation. ICG visualization of landmark arteries may help avoid vascular injuries during endoscopic sinus and skull base surgeries, particularly of AEA, PNA and ICA.

Symptom-Based Opioid-Free Treatment for Persistent Postoperative Headache After Vestibular Schwannoma Resection via the Retrosigmoid Approach.

OBJECTIVE: Postoperative headache (POH) is a disturbing symptom following vestibular schwannoma (VS) resection. However, there are currently no treatment guidelines. The aim of this study was to evaluate the usefulness of symptom-based opioid-free treatments for persistent POH following VS resection. METHODS: Of 137 patients in whom sporadic VS was resected via the retrosigmoid approach, 74 had persistent POH beyond 3 postoperative months. Their symptoms were classified as tension-type headache, migraine, neuralgia, or other and were treated. We retrospectively analyzed the treatment outcomes during 2 postoperative years. RESULTS: Patients with persistent POH were significantly younger (P = 0.003) and had significantly smaller tumors (P = 0.001) and greater extent of resection (P = 0.04) than patients without POH. The most common simple symptom was tension-type headache in 56 patients, followed by migraine in 6 patients and neuralgia in 5 patients. All 7 patients with complex symptoms had a mixture of tension-type headache and migraine. Complete disappearance of POH was achieved in 40 (54%) patients, and a medication-free condition was achieved in 51 (69%). No patients had residual severe POH that could not be controlled with medication. Achievement of a medication-free outcome that included complete disappearance of persistent POH was significantly more common in patients with preserved facial nerve function (P = 0.008) and patients with simple symptoms (P < 0.001). CONCLUSIONS: A symptom-based approach is appropriate for understanding and managing persistent POH after VS resection with excellent pain control. Preserved facial nerve function and simple symptoms are significant prognostic factors for a medication-free outcome.

Glutamic Acid and Total Creatine as Predictive Markers for Epilepsy in Glioblastoma by Using Magnetic Resonance Spectroscopy Before Surgery.

OBJECTIVE: Epilepsy in glioblastoma patients significantly reduces their quality of life; however, little is known about the association between predicting epilepsy and metabolites in tumors. In this study, we used 3.0-T magnetic resonance imaging and 1H-magnetic resonance spectroscopy (MRS) to quantify metabolite concentrations in patients with varying epilepsy histories. METHODS: Fifty-one patients with glioblastoma underwent pretreatment 3.0-T MRI/1H-MRS scanning. Single-voxel (1.5 cm3) MRS, in an enhanced lesion, was acquired using a double-echo point-resolved spectroscopic sequence with chemical-shift selective water suppression. MRS data were quantified with linear combination model (LC-Model) software. We compared the MRS data between groups with and without epilepsy during the postoperative course (EP). RESULTS: The ratios of glutamate (Glu) and glutamate + glutamine (Glx) to total creatine (Glu/tCr and Glx/tCr) in the tumor were associated with epilepsy history. The receiver operating characteristic curve analysis showed that a Glu/tCr value of 1.81 was 70% sensitive and 90% specific for the prediction of EP (area under curve: 0.82). In the analysis excluding patients with preoperative epilepsy, a Glu/tCr value of 1.81 was 75% sensitive and 88% specific for the prediction (area under curve: 0.87). CONCLUSIONS: Intratumoral metabolite concentrations measured using pretreatment 3.0-T MRI/1H-MRS changed characteristically in the group with EP. Our study suggests that the Glu/tCr ratio in tumors has adequate reliability in predicting EP. Pretreatment MRS is a minimally invasive and simple procedure that can provide useful information on glioblastoma patients.

Contribution of Endoplasmic Reticulum Stress to the Clinical Instability of Carotid Plaques in Human Carotid Stenosis.

Endoplasmic reticulum (ER) stress is an important process during the progression of atherosclerosis. The aim of this study was to elucidate the association of ER stress and clinical instability of carotid plaque. One hundred ninety-three patients with carotid stenosis undergoing carotid endarterectomies (CEAs) were enrolled. We classified the patients into 3 groups: the asymptomatic, symptomatic, and cTIA (crescendo transient ischemic attack)/SIE (stroke in evolution) groups. Immunohistological staining was performed to assess ER stress and apoptosis. The correlation between ER stress marker expression and clinical instability was analyzed by Tukey-Kramer test and ordinal logistic regression. From the 193 CEAs, 24 asymptomatic plaques and 24 symptomatic plaques were randomly selected, and all 7 plaques in the cTIA/SIE group were selected. Glycophorin A staining demonstrated significant correlation between intraplaque hemorrhage and clinical instability (odds ratio [OR], 1.27; 95%CI, 1.14-1.41). The expression of ER stress markers (glucose-regulated protein 78 [GRP78] and C/EBP homologous protein [CHOP]) exhibited a significant correlation with clinical instability (GRP78: OR, 1.25; 95%CI, 1.14-1.38, CHOP: OR, 1.39; 95%CI, 1.16-1.66). Double-label immunofluorescence demonstrated ER stress markers were detected in CD68-positive cells and smooth muscle actin (SMA)-positive cells. The coexpression of the ER stress markers exhibited a significant correlation with clinical instability (CD68/GRP78: OR, 1.13; 95%CI, 1.05-1.20, CD68/CHOP: OR, 1.092; 95%CI, 1.04-1.14, SMA/CHOP: OR, 1.082; 95%CI, 1.04-1.13). However, the colocalization of CHOP and cleaved caspase-3 (apoptosis marker) did not correlate with clinical instability. These findings indicated that the ER stress pathway may be a potential therapeutic target in the prevention of stroke.

Geranylgeranylacetone attenuates cerebral ischemia-reperfusion injury in rats through the augmentation of HSP 27 phosphorylation: a preliminary study.

BACKGROUND: We previously reported that heat shock protein 27 (HSP27) phosphorylation plays an important role in the activation of glucose-6-phosphate dehydrogenase (G6PD), resulting in the upregulation of the pentose phosphate pathway and antioxidant effects against cerebral ischemia-reperfusion injury. The present study investigated the effect of geranylgeranylacetone, an inducer of HSP27, on ischemia-reperfusion injury in male rats as a preliminary study to see if further research of the effects of geranylgeranylacetone on the ischemic stroke was warranted. METHODS: In all experiments, male Wistar rats were used. First, we conducted pathway activity profiling based on a gas chromatography-mass spectrometry to identify ischemia-reperfusion-related metabolic pathways. Next, we investigated the effects of geranylgeranylacetone on the pentose phosphate pathway and ischemia-reperfusion injury by real-time polymerase chain reaction (RT-PCR), immunoblotting, and G6PD activity, protein carbonylation and infarct volume analysis. Geranylgeranylacetone or vehicle was injected intracerebroventricularly 3 h prior to middle cerebral artery occlusion or sham operation. RESULTS: Pathway activity profiling demonstrated that changes in the metabolic state depended on reperfusion time and that the pentose phosphate pathway and taurine-hypotaurine metabolism pathway were the most strongly related to reperfusion among 137 metabolic pathways. RT-PCR demonstrated that geranylgeranylacetone did not significantly affect the increase in HSP27 transcript levels after ischemia-reperfusion. Immunoblotting showed that geranylgeranylacetone did not significantly affect the elevation of HSP27 protein levels. However, geranylgeranylacetone significantly increase the elevation of phosphorylation of HSP27 after ischemia-reperfusion. In addition, geranylgeranylacetone significantly affected the increase in G6PD activity, and reduced the increase in protein carbonylation after ischemia-reperfusion. Accordingly, geranylgeranylacetone significantly reduced the infarct size (median 31.3% vs 19.9%, p = 0.0013). CONCLUSIONS: As a preliminary study, these findings suggest that geranylgeranylacetone may be a promising agent for the treatment of ischemic stroke and would be worthy of further study. Further studies are required to clearly delineate the mechanism of geranylgeranylacetone-induced HSP27 phosphorylation in antioxidant effects, which may guide the development of new approaches for minimizing the impact of cerebral ischemia-reperfusion injury.

Anatomical variation of the internal carotid artery and its implication to the endoscopic endonasal translacerum approach.

BACKGROUND: The endoscopic endonasal trans-lacerum approach (EETLA) is useful in handling skull base tumors around inferior petrous apex (IPA); however, its surgical corridor is exclusively a triangular space (supra-eustachian triangle [SET]), between the internal carotid artery (ICA) and eustachian tube. METHODS: We investigated correlation between SET size and extent of resection around the IPA (lateral extent of resection [EOR]) through a retrospective analysis of 15 surgeries using EETLA. RESULTS: Of 15 cases (9 chordomas, 4 chondrosarcomas, and 2 meningiomas), 20 sides of IPA were affected by the tumor. When being restricted to sides with severe lateral tumor extension beyond the midpoint of petrous ICA (10 sides), the SET size was significantly broader in the group with lateral EOR of ≥90% (p value = 0.019). CONCLUSIONS: The SET size was a powerful index of tumor resectability in EETLA, especially in cases with severe tumor extension. The individual anatomical variations should be considered when determining EETLA application.

Glioma cells require one-carbon metabolism to survive glutamine starvation.

Cancer cells optimize nutrient utilization to supply energetic and biosynthetic pathways. This metabolic process also includes redox maintenance and epigenetic regulation through nucleic acid and protein methylation, which enhance tumorigenicity and clinical resistance. However, less is known about how cancer cells exhibit metabolic flexibility to sustain cell growth and survival from nutrient starvation. Here, we find that serine and glycine levels were higher in low-nutrient regions of tumors in glioblastoma multiforme (GBM) patients than they were in other regions. Metabolic and functional studies in GBM cells demonstrated that serine availability and one-carbon metabolism support glioma cell survival following glutamine deprivation. Serine synthesis was mediated through autophagy rather than glycolysis. Gene expression analysis identified upregulation of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) to regulate one-carbon metabolism. In clinical samples, MTHFD2 expression was highest in the nutrient-poor areas around "pseudopalisading necrosis." Genetic suppression of MTHFD2 and autophagy inhibition caused tumor cell death and growth inhibition of glioma cells upon glutamine deprivation. These results highlight a critical role for serine-dependent one-carbon metabolism in surviving glutamine starvation and suggest new therapeutic targets for glioma cells adapting to a low-nutrient microenvironment.

Acute Occlusion of the Ventriculoperitoneal Shunt Due to Factor XIII Deficiency-related Postoperative Hemorrhage: A Case Report.

Coagulation factor XIII (F13) deficiency has been known to be a rare disease with estimated one per two million and one of the possible reasons of postoperative hemorrhage; however, it still remains unpenetrated to physicians. We report a case of acute ventriculoperitoneal (VP) shunt dysfunction due to delayed intraventricular hemorrhage, which could be because of F13 deficiency. The patient was a 48-year-old man with a history of post-meningitis hydrocephalus followed by VP shunt placement. He was found unconscious and transferred to our hospital. A brain CT scan demonstrated shunt malfunction, and he underwent emergency shunt revision. The postoperative course was uneventful except for unexpected neck bruises and continuous minor bleeding from the surgical wound. Three days after surgery, he suddenly became comatose and a CT scan revealed the recurrence of hydrocephalus with newly identified small volume of intraventricular hemorrhage. Emergency shunt revision was performed again. The shunt valve was filled with a hematoma and bloody cerebrospinal fluid was drained from the ventricle. Postoperative blood sample examination demonstrated no abnormal findings but a decreased level of F13 activity, which was thought to be a possible cause of postoperative hemorrhage and the shunt valve hematoma. F13 deficiency causes delayed intracranial hemorrhage 24-48 h after neurological surgery. It can only be diagnosed by checking F13 activity with suspicion. If diagnosed accurately beforehand, unexpected postoperative bleeding can be preventable with proper treatment, such as F13 concentrate and cryoprecipitate. The actual number of the patient with F13 deficiency may be more than estimated ever.

[Sellar and Parasellar Inflammatory Lesions with Impaired Visual Function:Clinical Features and Endoscopic Surgical Outcomes of Six Cases].

Accurate diagnosis and treatment of sellar and parasellar inflammatory lesions is difficult. We report six patients with sellar and parasellar inflammatory lesions and impaired visual function, who underwent endonasal endoscopic surgery. These patients included one with aspergillosis, one with hypertrophic pachymeningitis, one patient with abscess, and three with idiopathic granulomatous lesions. Following surgery and medication, visual function improved in patients with aspergillosis, hypertrophic pachymeningitis, and abscess. In patients with idiopathic granulomatous inflammation, visual function improved in one out of three patients. The treatment outcome for sellar and parasellar inflammatory lesions with impaired visual function depends on the surgery as well as on the reaction to postoperative medication. In the present study, the functional prognosis of patients with idiopathic granulomatous lesions was relatively poor when compared with that of patients with other inflammatory lesions.

Submucosal Inferior Turbinectomy to Widen the Surgical Corridor for Endoscopic Endonasal Skull Base Surgery.

The nasal cavity is the exclusive surgical corridor for endoscopic endonasal surgery; however, it is sometimes too narrow to allow extensive surgical maneuvering. Here we show the technique of submucosal inferior turbinectomy (SIT) to widen this surgical corridor. Its effectiveness is evaluated quantitatively by comparing pre- and intraoperative magnetic resonance images. Between March 2015 and October 2018, we performed endoscopic endonasal resection of 57 skull base tumors with 3T intraoperative magnetic resonance imaging (iMRI). Among these resections, cases with previous endonasal surgery and cases for which the iMRI did not cover the entire nasal cavity were excluded. Finally, six cases with and 19 cases without SIT were included in the subsequent retrospective analysis. We measured the dimensions of the narrowest area in inferior nasal cavity on pre- and intraoperative coronal plane gadolinium (Gd)-enhanced T1-weighted MR images using dedicated software, and compared them. The incidence rates of postoperative nasal complaints at outpatient clinics were also compared. Considerable widening of the inferior nasal cavity could be achieved with the SIT, which was statistically significant compared with those without the SIT (111.1 ± 56.5% vs. 39.4 ± 59.4%, respectively; P = 0.0093). In terms of the incidence rate of postoperative nasal complaints at 6 months, there was no statistical difference between the groups (33.3% vs. 15.8%, respectively; P = 0.35). SIT is effective for widening the surgical corridor while keeping nasal function and is especially helpful for lower clivus and laterally extended skull base lesions.

Transvenous embolization through the ipsilateral deep facial vein: A novel approach route for treatment of a cavernous sinus dural arteriovenous fistula.

The superior ophthalmic vein (SOV) approach through the facial vein is usually preferred for transvenous embolization of a cavernous sinus dural arteriovenous fistula (CS DAVF) when the ipsilateral inferior petrosal sinus is angiographically occluded. However, navigating the microcatheter can sometimes be difficult because of stenosis or tortuous angulation at the junction between the angular vein and SOV. We present a novel transvenous access route to treat a CS DAVF using the ipsilateral deep facial vein through the SOV to reach the cavernous sinus. A 66-year-old woman presented with left-sided chemosis, exophthalmos, and external ophthalmoplegia. Angiography showed a left CS DAVF associated with a dilated SOV and retrograde cortical venous reflux. A dilated drainage vein, which branched from the SOV, ran through the lateral aspect of the orbit and exited the orbit through the inferior orbital fissure. This vein connected with the ipsilateral deep facial vein draining into the facial and internal jugular veins. We performed transvenous embolization via the SOV approach through the deep facial vein and achieved complete obliteration, by placing 3 platinum coils, without complications. Ophthalmic veins may connect with the cavernous sinus and pterygoid plexus, passing through the superior and inferior orbital fissures, respectively. Our case suggests that the deep facial vein may provide access to the SOV through the inferior orbital fissure without passing the difficult tortuous angle between the angular vein and SOV.

Refractory communicating hydrocephalus after radiation for small vestibular schwannoma with asymptomatic ventriculomegaly: A case report.

Communicating hydrocephalus is a known tumor-related syndrome associated with vestibular schwannoma, which can occur even in small tumor. Radiation has become a popular primary treatment option for small schwannoma; however, little is known about the efficacy and risk accompanying asymptomatic ventriculomegaly on images. We report a case of a 59-year-old woman who suffer from refractory communicating hydrocephalus after radiation for small vestibular schwannoma with asymptomatic ventriculomegaly. After the surgical removal of the tumor, hydrocephalus was gradually improved due to intermittent lumbar puncture and finally resolved without shunt placement. Surgical removal should be considered as the first option for the treatment, even if the patient is asymptomatic and the images revealed a small vestibular schwannoma with only slight ventricular enlargement.

Intraoperative 3-T Magnetic Resonance Spectroscopy for Detection of Proliferative Remnants of Glioma.

BACKGROUND: Few studies have examined the usefulness of intraoperative magnetic resonance spectroscopy (iMRS) for identifying abnormal signals at the resection margin during glioma surgery. The aim of this study was to assess the value of iMRS for detecting proliferative remnants of glioma at the resection margin. METHODS: Fifteen patients with newly diagnosed glioma underwent single-voxel 3-T iMRS concurrently with intraoperative magnetic resonance imaging-assisted surgery. Volumes of interest (VOIs) were placed at T2-hyperintense or contrast-enhancing lesions at the resection margin. In addition to technical verification, the correlation between the MIB-1 labeling index (a pathologic feature) and metabolites measured using iMRS (N-acetyl-L-aspartate [NAA], choline [Cho], and Cho/NAA ratio) was analyzed. RESULTS: iMRS was performed for 20 VOIs in 15 patients. Fourteen (70%) of these VOIs were confirmed to be MIB-1-positive. There was a significant positive correlation between the Cho/NAA ratio and MIB-1 index (r = 0.46, P = 0.04). Cho level (P = 0.003) and Cho/NAA ratio (P = 0.002) were significantly higher in VOIs that were MIB-1-positive than in those that were MIB-1-negative. Detection of a Cho level >1.074 mM and a Cho/NAA ratio >0.48 using iMRS resulted in high diagnostic accuracy for MIB-1-positive remnants (Cho level: sensitivity 86%, specificity 100%; Cho/NAA ratio: sensitivity 79%, specificity 100%). CONCLUSIONS: This study provides evidence that 3-T iMRS can detect proliferative remnants of glioma at the resection margin using the Cho level and Cho/NAA ratio, suggesting that intraoperative magnetic resonance imaging-assisted surgery with iMRS would be practicable in glioma.

Comparative Evaluation of 3-Dimensional High Definition and 2-Dimensional 4-K Ultra-High Definition Endoscopy Systems in Endonasal Skull Base Surgery.

BACKGROUND: The differences between 3-dimensional (3D) high definition (HD) and 2-dimensional (2D) 4-K ultra-HD (4K) endoscopy and their respective advantages remain unclear. OBJECTIVE: To evaluate the utility of these endoscopy systems in endonasal skull base surgery. METHODS: Consecutive series of endoscopic endonasal surgeries performed after introduction of 3D/HD and 2D/4K systems (July 2017) were retrospectively evaluated. Sporadic cases treated with either system, or a conventional 2D standard definition (SD) system, during the rental period from March 2016 were also included. Objective comparisons between the systems were made for newly diagnosed Knosp grade 0 to 3 pituitary adenomas. Surgical procedures were divided into nasal, sphenoidal, and intradural phases, and the surgical procedural time was compared for each phase. The time required for and accuracy of suturing the sellar floor dura was also evaluated. RESULTS: A total of 74 cases were treated with 3D/HD and/or 2D/4K, and 12 cases with 2D/SD. 3D/HD was advantageous in the nasal phase because of its intuitive depth perception. 2D/4K was advantageous in the intradural phase because of its superior image quality. Surgical time of the nasal phase with 3D/HD, and that of the intradural phase with 2D/4K, were significantly shorter than that with 2D/SD. The time required for and accuracy of sellar floor dural suturing showed a trend toward improving in the order of 2D/SD, 2D/4K, and 3D/HD. CONCLUSION: 3D/HD and 2D/4K endoscopy systems have different advantages, which are useful in distinct surgical phases. Understanding the characteristics of endoscopy systems is important for selecting the most appropriate system for distinct surgical situations.

Machine Learning to Predict In-Hospital Morbidity and Mortality after Traumatic Brain Injury.

Recently, successful predictions using machine learning (ML) algorithms have been reported in various fields. However, in traumatic brain injury (TBI) cohorts, few studies have examined modern ML algorithms. To develop a simple ML model for TBI outcome prediction, we conducted a performance comparison of nine algorithms: ridge regression, least absolute shrinkage and selection operator (LASSO) regression, random forest, gradient boosting, extra trees, decision tree, Gaussian naïve Bayes, multi-nomial naïve Bayes, and support vector machine. Fourteen feasible parameters were introduced in the ML models, including age, Glasgow Coma Scale (GCS), systolic blood pressure (SBP), abnormal pupillary response, major extracranial injury, computed tomography (CT) findings, and routinely collected laboratory values (glucose, C-reactive protein [CRP], and fibrin/fibrinogen degradation products [FDP]). Data from 232 patients with TBI were randomly divided into a training sample (80%) for hyperparameter tuning and validation sample (20%). The bootstrap method was used for validation. Random forest demonstrated the best performance for in-hospital poor outcome prediction and ridge regression for in-hospital mortality prediction: the mean statistical measures were 100% sensitivity, 72.3% specificity, 91.7% accuracy, and 0.895 area under the receiver operating characteristic curve (AUC); and 88.4% sensitivity, 88.2% specificity, 88.6% accuracy, and 0.875 AUC, respectively. Based on the feature selection method using the tree-based ensemble algorithm, age, Glasgow Coma Scale, fibrin/fibrinogen degradation products, and glucose were identified as the most important prognostic factors for poor outcome and mortality. Our results indicate the relatively good predictive performance of modern ML for TBI outcome. Further external validation is required for more heterogeneous samples to confirm our results.

Application of a Minimally Invasive Liposuction Technique for Harvesting Fat during Transsphenoidal Surgery: A Technical Note.

Secure reconstruction in transsphenoidal surgery (TSS) is important for the prevention of the major and serious complication of postoperative cerebrospinal fluid (CSF) leak. Although abdominal fat can be safely and effectively used as a reconstruction tissue, harvesting it from the abdominal wall is traumatic and invasive, resulting in cosmetic problems. In this report, we present a method of harvesting abdominal fat using a minimally invasive liposuction technique to avoid cosmetic issues. Since 2016, we have been using fat harvested from the abdominal wall by suctioning with a dedicated syringe for reconstruction after TSS in selected cases. The liquefied fat obtained by the liposuction technique was wrapped with an oxycellulose sheet and changed its form to what we termed "fatty candy". In this form, the fat maintained its configuration and could be handled almost as easily as a conventional fat graft. In our experienced series, there was no case with wound complication nor postoperative or late-onset CSF leak during a postoperative follow-up of at least 3 months. The fat harvested by this simple and minimally invasive liposuction technique can be expected to provide an autologous graft that is adequate not only for prevention of cosmetic problems but also for prevention of postoperative CSF leak.

Pentose phosphate pathway activation via HSP27 phosphorylation by ATM kinase: A putative endogenous antioxidant defense mechanism during cerebral ischemia-reperfusion.

Molecular mechanism underlying ischemic stroke remains poorly understood. We previously reported glucose 6-phosphate dehydrogenase (G6PD) activity in pentose phosphate pathway (PPP) is activated via heat shock protein 27 (HSP27) phosphorylation at serine 85 (S85) by ataxia telangiectasia mutated (ATM) kinase during cerebral ischemia. This mechanism seems to be endogenous antioxidative system. To determine whether this system also works during reperfusion, we performed comparative metabolic analysis of reperfusion effect on metabolism in rat cortex using middle cerebral artery occlusion (MCAO). Metabolic profiling using gas-chromatography/mass-spectrometry analysis showed changes in metabolic state that depended on reperfusion time. Enrichment analysis showed PPP was significantly upregulated during ischemia-reperfusion. Significant increases in fructose 6-phosphate and ribulose 5-phosphate after reperfusion also suggested enhancement of PPP. In relation to PPP, ischemia-reperfusion induced an increase of up to 69-fold in HSP27 transcripts after 24-h reperfusion. Immunoblotting showed gradual increase in HSP27 protein and marked increase in HSP27 phosphorylation (S85) that were time-dependent (4.5-fold after 24-h reperfusion). G6PD activity was significantly elevated after 1-h MCAO (20%), reduced after 1-h reperfusion, increased gradually thereafter and significantly elevated after 24-h reperfusion. The NADPH/NAD+ ratio displayed similar increasing pattern. Intracerebroventricular injection of ATM kinase inhibitor (KU-55933) significantly reduced HSP27 phosphorylation and G6PD activity, significantly increased protein carbonyl, and resulted in increase in infarct size (100%) 24-h after reperfusion following 90-min MCAO. Consequently, G6PD activation via HSP27 phosphorylation by ATM kinase may be part of endogenous antioxidant defense neuroprotection mechanism that is activated during ischemia-reperfusion. These findings have important implications for treatment of stroke.

Endoscopic endonasal surgery for pituitary adenomas extending to the oculomotor cistern.

BACKGROUND: Extension of a pituitary adenoma to the oculomotor cistern harbors the risk of oculomotor nerve impairment and further extension into the interpeduncular cistern. The role of endoscopic endonasal surgery for those lesions was investigated. METHODS: The medical records were retrospectively analyzed. Attention was paid to the oculomotor nerve function and removal rate of the tumor within the oculomotor and interpeduncular cisterns. RESULTS: Six patients were eligible for the study, including 2 with oculomotor nerve palsy. The tumor from the oculomotor and interpeduncular cistern was removed in all except on one side of the case with bilateral tumor extension. The oculomotor nerve palsy demonstrated partial recovery in both cases during the 3-month follow-up. CONCLUSION: The pituitary adenoma extending to the oculomotor cistern can be removed under the endoscope. Improvement of oculomotor nerve palsy can be achieved, and further tumor extension into the interpeduncular cistern can be prevented.

Successful cerebral thrombectomy for a nonagenarian with stroke in the subacute phase after transcatheter aortic valve implantation.

BACKGROUND: Thromboembolic events are infrequent but serious complications of transcatheter aortic valve implantation (TAVI), occurring in 2.3-10% of the patients. However, the cause of post-TAVI stroke is unclear. CASE DESCRIPTION: A 90-year-old female underwent transfemoral-TAVI for severe aortic stenosis. Ten days later, she presented with an ischemic stroke of the left middle cerebral artery territory due to new-onset atrial fibrillation (NOAF). She underwent emergent endovascular thrombectomy with good reperfusion approximately 6 hours after onset of symptoms. At hospital discharge, her National Institutes of Health Stroke Scale score was 11. CONCLUSIONS: Although NOAF is rare during the subacute phase of TAVI, in this patient it might be the cause of her stroke. This finding suggests that dual antiplatelet therapy alone may be insufficient in the prevention of stroke after TAVI. Nonetheless, this case demonstrates the efficacy and safety of endovascular thrombectomy in patients with acute ischemic stroke caused by NOAF after TAVI.